Less Alzheimer disease neuropathology in medicated hypertensive than nonhypertensive persons

Hoffman LB, Schmeidler J, Lesser GT, Beeri MS, Purohit DP, Grossman HT, et al.; Neurology 2009; 72 (20); 1720-1726. [Epub 2009 Feb 18]

Commented by Prof Serge Gauthier, 9 Jun 2009

Aim of the study

To test the hypothesis that the use of antihypertensive medications is associated with lower Alzheimer disease (AD) pathology.

Method

Post-mortem examination of 291 brains collected over 20 years by the Mount Sinai School of Medicine Department of Psychiatry Brain Bank, from New York City area nursing homes. Inclusion criteria were age 60 or more, normal brain examination or only AD pathology.

A pre-mortem Clinical Dementia Rating Score (CDR) was obtained by questioning the staff and families about the 6 months prior to death. The presence of hypertension and its treatment were ascertained by chart review. Neuritic plaques (NP) and neurofibrillary tangles (NFT) densities were quantified using the CERAD neuropathological criteria.

Medicated hypertensives (HTN-med), non medicated hypertensives (HTN-nomed) and patients with no hypertension (no-HTN) were compared by analysis of variance.

Results

The HTN-med group had significantly less AD neuropathology than the no-HTN group, who had over 50% higher mean NP and NFT ratings, and double the NP count of the HTN-med group. The HTN-nomed group had significantly more neuropathology than the HTN-med group. The HTN-med group had the lowest level of dementia as reflected by the lowest pre-mortem CDR.

Professor Gauthier's comments

The authors interpret their findings as consistent with protective effects of antihypertensive medications against AD neuropathology. The caviat is that in late life (>70 years) contrary to mid-life, mild hypertension appears to be protective against dementia. Hypotension may be actually harmful in late life.

An accompanying article by Haag et al. (ref. 1) using a prospective population-based cohort for incident dementia also confirmed an 8% reduction of risk of dementia per year of use of antihypertensives for persons ≤ 75 years.

An accompanying editorial by David Knopman (ref. 2) highlight the facts that antihypertensive drugs may reduce the risk of dementia not only because of their protective effects on cerebro-vascular disease but also because of their actions on AD neuropathology.

The practical message is to treat hypertension adequately using pharmacologic and life-style changes up to age 75, but watch for hypotension as people age or progress through AD, since blood pressure tends to drift down in later stages of dementia.